Phase IV Study of the Safety and Efficacy of Everolimus in Adult Patients With Progressive pNET in China: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase IV Study of the Safety and Efficacy of Everolimus in Adult Patients With Progressive pNET in China (NCT02842749), a na phase 4 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The central statistical question is descriptive: how many participants in the safety population were recorded as having adverse events during the specified treatment and follow-up period? The record reports 61 participants at risk for the on-treatment adverse-event summaries. It lists 17 participants with serious adverse events and 60 with other adverse events in that period. These counts describe the treated study group, not a contrast between groups.

The trial enrolled 61 participants and is marked completed. Because there is no control arm, the study cannot separate outcomes associated with treatment from outcomes that might also occur because of the disease, other conditions, or circumstances not captured in the record. The results can characterize the observations recorded in this study, but do not by themselves establish a causal treatment effect.

3. Trial Design

This was a Phase IV, open-label, multicenter, single-arm study of everolimus in adults in China with locally advanced, unresectable or metastatic, well differentiated, progressive pancreatic neuroendocrine tumors. The registry lists an enrollment of 61 and a completed status. All participants were assigned to the everolimus group; there was no randomized allocation or masking.

The treatment instructions specified a starting dose of 10 mg orally once daily. Dose adjustments were allowed so that a participant could continue study treatment. The registry record does not describe a separate comparator, a placebo group, or a treatment assignment process beyond the single-arm design. Consequently, observed outcomes are not estimates of a between-group difference.

The primary outcome was the number of participants with treatment-emergent adverse events and serious adverse events. Its timeframe began with the first dose and continued until the end of study treatment plus a follow-up period of 30 days, up to a maximum duration of approximately 5 years. The safety population included participants who received at least one study treatment, analyzed according to the treatment actually received. The adverse-event summaries list 61 at risk during on-treatment follow-up.

Overall survival and progression-free survival assessed by investigators according to RECIST 1.1 are named as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. The record lists three outcome measures and no statistical analyses. Details of the protocol’s sample-size justification, planned interim analyses, and statistical analysis plan are not reported in the registry record.

A single-arm design is suited to describing events observed among treated participants, but it does not supply a contemporaneous estimate of what would have happened under a different treatment. The open-label design also means that treatment was not masked. Those features are important context when reading the event counts and when considering how far the results can be generalized.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set (SS): including all participants who received at least one study treatment. Participants were analyzed according to the treatment they actually received.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 30 days, up to a maximum duration of approximately 5 years..

The primary outcome counts participants who experienced treatment-emergent adverse events and serious adverse events. The registry description includes any adverse event regardless of seriousness, serious events, events of grade 3 or 4, and events suspected to be related to study drug. The reported measure is a count of participants, rather than a count of every event episode.

The outcome’s timeframe starts at the first study-treatment dose and extends through the end of treatment plus a follow-up period of 30 days, up to a maximum duration of approximately 5 years. This defines the period during which events are included in the treatment-emergent safety summary. The Safety Analysis Set consists of participants who received at least one study treatment and is analyzed according to treatment actually received.

Counting affected participants is a direct way to describe how many people in the treated group had recorded events. Seriousness and severity categories add context because an event classified as serious is not interchangeable with any event, and a grade 3 or 4 event is a distinct category in the outcome description. Suspected relationship to study drug is also a recorded classification, not proof that treatment caused an event.

As a general statistical point, a count is useful for describing observed safety experience but does not express the timing, duration, recurrence, or comparative risk of events unless those quantities are separately reported. The registry record does not report numerical results for every component named in the primary outcome description. The posted counts should therefore be read as the specific reported summaries, not as a complete account of every possible safety measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a participant-count outcome: it records whether participants experienced specified adverse-event categories. The study’s safety population is defined as participants receiving at least one study treatment, with analysis according to treatment actually received. This population definition matters because a safety summary generally concerns exposure to treatment, rather than every person who may have been enrolled or screened.

What does a participant count describe?

A participant count answers how many people in the defined analysis population were recorded with an outcome during the specified observation period. It is not the same as a count of event episodes: one participant may experience more than one event, but a participant-level count still counts that person as a participant with the outcome. The primary outcome description includes any adverse event, serious adverse events, grade 3 or 4 events, and events suspected to be related to study drug. The registry record does not report numerical values for every one of these categories.

The on-treatment summaries identify 61 participants at risk, 17 with serious adverse events, and 60 with other adverse events. The record does not report confidence intervals for these counts. General statistical context: an interval estimate can convey uncertainty about a population quantity beyond the observed study group, but its interpretation depends on the estimator and assumptions used. A count alone should not be read as a guarantee of the frequency in another population.

Why does the design matter for interpretation?

This is a single-arm, open-label study with no randomized comparator. A randomized comparison can, under appropriate conduct and analysis, estimate differences between assigned groups while reducing some sources of confounding. Here there is no second group against which to estimate a treatment contrast. The outcome counts are therefore descriptive. They cannot show whether event frequency differs from what would have occurred with another intervention or without study treatment.

Open-label means treatment masking was absent. As a general matter, knowledge of treatment can affect reporting, assessment, or decisions about care. That possibility is relevant to interpretation, but the registry record does not document a particular bias or quantify its impact. The study’s design should be treated as a limit on causal interpretation, not as proof that any specific event assessment was inaccurate.

What does the event timeframe contribute?

The primary outcome period begins with the first dose and continues until the end of study treatment plus a follow-up period of 30 days, up to a maximum duration of approximately 5 years. Defining a window makes clear which events qualify for the treatment-emergent summary. It does not by itself explain how long each participant was observed, whether follow-up was complete, or how missing observations were handled; those details are not reported in the registry record.

General statistical context: when participants have unequal observation time, a simple participant count does not convey an event rate per unit of time. Time-to-event methods can account for the timing of an outcome and censoring, but no numerical survival or progression-free survival results or corresponding statistical analyses are reported in the registry record. The named secondary outcomes are overall survival and investigator-assessed progression-free survival according to RECIST 1.1.

How should uncertainty and planning illustrations be read?

General statistical context: a p-value, when reported, measures how compatible observed data are with a specified null model; it is not the probability that a treatment works or that a result is true. A confidence interval describes a range of values compatible with data and an estimation procedure, subject to its assumptions. Neither provides a substitute for a suitable comparison group. No statistical analyses are listed in the registry record, and no p-values or confidence intervals for the reported safety counts are given.

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with a target effect expressed as a fraction of an observed effect. These are planning assumptions, not the trial’s reported design justification. The illustrations are not observed power and do not turn this single-arm study into a two-arm comparison. The registry record does not report the protocol’s sample-size justification or state that these illustration assumptions governed the trial.

General statistical context: over-dispersion occurs when variation in outcomes is greater than a model assumes. If present, it can make standard errors too small and confidence intervals too narrow under an unsuitable model. Whether over-dispersion was assessed or relevant to any planned analysis is not reported in the registry record. Because the posted safety outcome is a participant count and the record lists no statistical analyses, a particular inferential model should not be inferred.

The record also does not report whether analyses were adjusted for baseline characteristics, how recurrent events were handled, or whether any prespecified sensitivity analyses were conducted. Such methods can matter for some estimands, but their absence from the registry record means no specific approach can be attributed to this trial. The most defensible reading is to use the posted counts as descriptive observations and keep their population, outcome definitions, and follow-up window in view.

10. Multiplicity, Missing Data and Analysis Populations

The registry record names the primary safety outcome and two secondary outcomes: overall survival and investigator-assessed progression-free survival according to RECIST 1.1. It lists three outcome measures and no statistical analyses. Numerical results for the secondary outcomes are not reported in the registry record.

When several outcomes are tested, multiplicity can increase the chance of at least one apparently unusual result if each is interpreted without accounting for the set of tests. Methods such as prespecifying a primary outcome or adjusting inference can address particular multiplicity concerns. The registry record does not report a multiplicity procedure, a hierarchy for testing outcomes, or an inferential plan. No such procedure should be assumed.

The registry record also does not report how missing outcome data were handled, whether participants were lost to follow-up, or whether any imputation or sensitivity analysis was used. These omissions matter because missingness can affect interpretation, especially for outcomes that depend on continued observation over time. The specified safety population includes participants who received at least one study treatment, but that definition does not itself describe the completeness of follow-up or the handling of missing event information.

For the reported adverse-event summaries, the at-risk denominator is 61 in the on-treatment category. The record does not provide further detail on participant-level missingness or observation time for each person. As a general statistical principle, complete-case summaries describe the data available under their analysis definitions; they do not automatically resolve potential bias if missingness is related to outcomes. The registry record does not state whether that issue was evaluated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infectious pneumonitis (4.9%), asthenia (3.3%), type 2 diabetes mellitus (1.6%), cachexia (1.6%), function liver abnormal (1.6%).

The on-treatment adverse-event summaries list 61 participants at risk, with 17 participants recorded in the serious adverse-event category and 60 in the other adverse-event category. The primary outcome concerns participants with events, so these are participant counts rather than a count of every event episode. The record’s primary-outcome description also includes grade 3 or 4 events and events suspected to be related to study drug, but it does not report numerical results for every category described.

The listed serious adverse-event terms are infectious pneumonitis, 4.9%; asthenia, 3.3%; type 2 diabetes mellitus, 1.6%; cachexia, 1.6%; function liver abnormal, 1.6%; and anal abscess, 1.6%. These percentages are reported as term-specific summaries. They should not be interpreted as proof of causation or as a complete list of all events unless the registry record establishes that completeness, which it does not.

Deaths are listed separately as 6 in the on-treatment category and 22 in survival follow-up. The record does not report their causes or establish a relationship to study drug. These figures describe the registry’s categories; they are not a randomized comparison and should not be treated as evidence of treatment effect.

12. What the Result Does, and Does Not, Mean

The results describe adverse events recorded among participants in a completed, open-label, single-arm study of everolimus. In the on-treatment safety summaries, 17 participants were recorded with serious adverse events and 60 with other adverse events among 61 at risk. Serious-event terms and their reported percentages are also listed. These observations characterize the study group and the registry’s event classifications.

They do not show what would have happened to the same participants under a different treatment or without study treatment. With no comparator arm, the study cannot estimate a between-group difference or isolate the contribution of treatment from other factors. The open-label design is additional context for interpreting event assessment, although the registry record does not quantify any resulting bias.

The record names overall survival and progression-free survival as secondary outcomes, but numerical results for those outcomes are not reported in the registry record. The posted safety counts therefore do not establish an efficacy result. Nor do the listed serious-event terms establish that everolimus caused those events; the record describes suspected relationship as one component of the primary safety outcome but does not give a term-by-term causal determination in the listed summaries.

General statistical context: observed data are informative about the participants and observation process from which they arise. Extending a descriptive result to a broader population requires considering eligibility, setting, follow-up, measurement, and uncertainty. The registry record identifies adults in China with progressive, well differentiated pancreatic neuroendocrine tumors, but does not provide enough information to assess every source of variation or transportability.

The appropriate conclusion is therefore limited: the posted record reports a set of safety counts and event terms for this study, while comparative effects, numerical survival outcomes, and a causal interpretation are not established by these data alone. The counts should be read with their stated population and timeframe rather than as a complete measure of risk in other settings.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the difference between describing outcomes and estimating comparative effects. The study enrolled 61 participants and used a single-arm, open-label design. Its posted adverse-event counts can describe what was recorded among treated participants, but there is no concurrent control group from which to estimate a treatment contrast.

The primary outcome is a count of participants with treatment-emergent adverse events and serious adverse events, with additional categories described for severity and suspected relationship to study drug. The outcome’s defined observation window and safety-population definition are essential to interpreting the counts. Without that context, a count can be mistaken for a rate, a causal effect, or a summary of every possible event.

The record also names overall survival and investigator-assessed progression-free survival as secondary outcomes. Their numerical results are not reported in the registry record. This shows why outcome labels alone do not answer a statistical question: interpretation depends on reported estimates, uncertainty, analysis populations, and methods, not only on the outcome’s name.

Planning illustrations can help readers understand hypothetical sample-size requirements under stated assumptions, but they are not observed power and are not evidence that a trial was designed around those assumptions. The registry record does not report its own sample-size justification. Keeping planning calculations separate from observed results prevents a hypothetical design exercise from being mistaken for a trial finding.

More broadly, this study is a useful reminder that precision, causal identification, and clinical meaning are distinct. A participant count is directly interpretable for the study population, while its uncertainty and relevance beyond that population require further context. A single-arm record can contribute descriptive safety information without answering comparative questions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The single-arm design is the central limitation for causal interpretation. No randomized comparator is listed, so the posted event counts cannot estimate how safety outcomes differ from those under another treatment or no treatment. The open-label design means treatment was not masked; the registry record does not describe methods to assess or mitigate possible effects of treatment awareness on event reporting or assessment.

The enrollment was 61, and the on-treatment summaries list 61 participants at risk. Counts from a study of this size describe the observed group, but the registry record does not report confidence intervals or other uncertainty estimates for those counts. Rare or less frequently observed events may not be characterized precisely by the posted summaries.

The registry record does not report numerical results for the named secondary outcomes of overall survival and investigator-assessed progression-free survival. It also does not report the protocol’s sample-size justification, a statistical analysis plan, interim analyses, multiplicity handling, missing-data methods, or sensitivity analyses. These omissions restrict assessment of how analyses were planned and how robust the results may be to alternative assumptions.

The record gives a maximum primary safety observation duration of approximately 5 years, but does not report participant-level follow-up duration or completeness. The separate death counts for on-treatment and survival follow-up are not accompanied by causes or a treatment-relationship assessment. The registry record therefore does not support further conclusions about those deaths.

Finally, the study population is described as adults in China with locally advanced, unresectable or metastatic, well differentiated, progressive pancreatic neuroendocrine tumors. The record does not establish how well these observations apply to populations outside that description. The limitations concern interpretation of the reported record; they do not establish that any particular bias or missingness occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase IV Study of the Safety and Efficacy of Everolimus in Adult Patients With Progressive pNET in China — NCT02842749.
• Registry record last updated 2025-02-10; status last verified 2025-01.
• Results first posted 2025-02-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed Phase IV, open-label, multicenter, single-arm study of everolimus in adults in China with progressive pancreatic neuroendocrine tumors. Enrollment was 61. Participants were instructed to start at 10 mg orally once daily, with dose adjustments permitted.

The primary outcome counted participants with treatment-emergent adverse events and serious adverse events. The on-treatment summaries list 61 participants at risk, 17 with serious adverse events, and 60 with other adverse events. Serious-event terms and percentages are reported. The record also lists 6 deaths on treatment and 22 during survival follow-up, without causes or treatment-relationship conclusions.

Overall survival and investigator-assessed progression-free survival are named as secondary outcomes, but numerical results are not reported in the registry record. The study has no comparator group, and the record lists no statistical analyses. Its posted results are descriptive and do not establish comparative safety or efficacy.